ArticleBMC cancer2016
ROR2 is epigenetically inactivated in the early stages of colorectal neoplasia and is associated with proliferation and migration.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Review
- ROR2 promotes epithelial-mesenchymal transition by hyperactivating ERK in melanoma.Journal of cell communication and signaling · 2023Article
- Pan-Tissue and -Cancer Analysis of ROR1 and ROR2 Transcript Variants Identify Novel Functional Significance for an Alternative Splice Variant of ROR1.Biomedicines · 2022Article
- Role of ROR2 in promoting gastric cancer metastasis by enhancing c-JUN-mediated MMP3 transcription.Annals of translational medicine · 2022Article
- CellPhy: accurate and fast probabilistic inference of single-cell phylogenies from scDNA-seq data.Genome biology · 2022Article
- ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation.Journal of biomedical science · 2021Article
- ROR2 Is Epigenetically Regulated in Endometrial Cancer.Cancers · 2021Article
- Review
- Expression, Prognosis and Gene Regulation Network of NFAT Transcription Factors in Non-Small Cell Lung Cancer.Pathology oncology research : POR · 2021Article
- ROR1 is upregulated in endometrial cancer and represents a novel therapeutic target.Scientific reports · 2020Article
- The WNT receptor ROR2 drives the interaction of multiple myeloma cells with the microenvironment through AKT activation.Leukemia · 2020Article
- ROR2 induces cell apoptosis via activating IRE1α/JNK/CHOP pathway in high-grade serous ovarian carcinoma in vitro and in vivo.Journal of translational medicine · 2019Article
- ROR2 modulates neuropathic pain via phosphorylation of NMDA receptor subunit GluN2B in rats.British journal of anaesthesia · 2019Article
- Intraflagellar transport 20 promotes collective cancer cell invasion by regulating polarized organization of Golgi-associated microtubules.Cancer science · 2019Article
- Targeting Receptor Kinases in Colorectal Cancer.Cancers · 2019Review
- NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL-mediated extrinsic signaling pathway.Cancer medicine · 2018Article
- MethylatedOncotarget · 2017Article
- Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update.Open biology · 2017Review
- Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.Translational oncology · 2017Article
- Validation of specificity of antibodies for immunohistochemistry: the case of ROR2.Virchows Archiv : an international journal of pathology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) is closely linked to Wnt signalling, with 94 % of cases exhibiting a Wnt related mutation. ROR2 is a receptor tyrosine kinase that is thought to repress β-catenin dependent Wnt signalling. Our study aims to determine if ROR2 is epigenetically silenced in CRC and determine if in vitro silencing of ROR2 potentiates Wnt signalling, and alters the proliferative, migratory or invasive potential of cells.
methodsROR2 expression was examined in CRC cell lines and patient adenomas using qRT-PCR, while COBRA and bisulphite sequencing was used to analyse ROR2 promoter methylation. 258 patient primary tumour samples from publicly available databases were also examined for ROR2 expression and methylation. In addition, the functional effects of ROR2 modulation were investigated in HCT116 cells following ROR2 siRNA knockdown and in RKO and SW620 cells following ectopic ROR2 expression.
resultsReduced ROR2 expression was found to correlate with ROR2 promoter hypermethylation in colorectal cancer cell lines, carcinomas and adenomas. ROR2 expression was downregulated in 76.7 % (23/30) of CRC cell lines with increasing ROR2 promoter hypermethylation correlating with progressively lower expression. Analysis of 239 primary tumour samples from a publicly available cohort also found a significant correlation between reduced ROR2 expression and increased promoter methylation. Methylation analysis of 88 adenomas and 47 normal mucosa samples found greater percentage of adenoma samples to be methylated. Additional analysis also revealed that adenoma samples with reduced ROR2 expression also possessed ROR2 promoter hypermethylation. ROR2 knockdown in the CRC cell line HCT116 significantly decreased expression of the β-catenin independent Wnt targets genes JNK and NFATC1, increased cellular proliferation and migration but decreased invasion. When ROR2 was ectopically expressed in RKO and SW620 cells, there was no significant change to either cellular proliferation or migration.
conclusionROR2 is frequently epigenetically inactivated by promoter hypermethylation in the early stages of colorectal neoplasia and this may contribute to colorectal cancer progression by increasing cellular proliferation and migration.
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